Abstract
The O-linked-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic and nuclear proteins regulates basic cellular functions and is involved in the aetiology of diabetes and neurodegeneration. This intracellular O-GlcNAcylation is catalyzed by a single O-GlcNAc transferase, OGT. Here we report a novel OGT, EOGT, responsible for extracellular O-GlcNAcylation. Although both OGT and EOGT are regulated by hexosamine flux, EOGT localizes to the lumen of the endoplasmic reticulum and transfers GlcNAc to epidermal growth factor-like domains in an OGT-independent manner. Loss of Eogt gives phenotypes similar to those caused by defects in the apical extracellular matrix. Dumpy (Dp), a membrane-anchored extracellular protein, is O-GlcNAcylated, and EOGT is required for Dp-dependent epithelial cell-matrix interactions. Thus, O-GlcNAcylation of secreted and membrane glycoproteins is a novel mediator of cell-cell or cell-matrix interactions at the cell surface.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylglucosamine / metabolism*
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Acylation
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Amino Acid Sequence
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Animals
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Cell Communication / genetics*
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Drosophila Proteins / chemistry
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / enzymology
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Drosophila melanogaster / genetics*
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Epidermal Growth Factor / chemistry
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Epidermal Growth Factor / genetics
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Epidermal Growth Factor / metabolism
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Epithelial Cells / cytology
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Epithelial Cells / metabolism*
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Extracellular Matrix Proteins / genetics
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Extracellular Matrix Proteins / metabolism*
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Hexosamines / metabolism
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Mice
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Molecular Sequence Data
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N-Acetylglucosaminyltransferases / chemistry
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N-Acetylglucosaminyltransferases / genetics
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N-Acetylglucosaminyltransferases / metabolism*
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Plasmids
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Protein Binding
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Protein Processing, Post-Translational / genetics
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Protein Structure, Tertiary
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RNA Interference
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Sequence Homology, Amino Acid
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Signal Transduction
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Transfection
Substances
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DPY protein, Drosophila
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Drosophila Proteins
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Extracellular Matrix Proteins
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Hexosamines
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Epidermal Growth Factor
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Eogt protein, Drosophila
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N-Acetylglucosaminyltransferases
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O-GlcNAc transferase
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Acetylglucosamine